Nabumetone, 4-(6'-methoxy-2'-naphthyl)-butan-2-one, is a well known non-steroidal antiinflammatory agent described for example in U.S. Pat. No. 4,420,639. While various synthesis procedures for its production have been proposed and studied, the most efficacious procedures utilize 2-bromo-6-methoxynaphthalene (also known as 6-bromo-2-methoxynaphthalene) as a key starting material or chemical intermediate. This product is usually formed by hydrodebromination of 1,6-dibromo-2-naphthol by use of iron powder in an aqueous acid medium to form 6-bromo-2-naphthol, followed by treatment with dimethyl sulfate and sodium hydroxide to effect methylation of the hydroxyl group. Unfortunately this process approach suffers from need for long cycle times, formation of large amounts of co-products from both reaction steps, need for use of stoichiometric excesses of dimethyl sulfate and iron, and lower than desired plant throughput. Another method of producing 2-bromo-6-methoxynaphthalene is suggested in U.S. Pat. No. 5,256,829 where hydrodebromination of 1,6-dibromo-2-naphthol to 6-bromo-2-naphthol is effected by use of hydrogen and a tungsten carbide-based catalyst in an acidic organic solvent, and where the reagents taught for use in the methylation step are methyl sulfate or methanol. Despite the intensity and scope of prior investigations of such process steps, a need exists for process technology capable of reducing the quantities of by-product wastes formed in the operation, of avoiding the need for use of excess iron and/or dimethyl sulfate as reaction components, and of improving the overall efficiency of plant operation when conducted on a large scale.
This invention is deemed to fulfill this need in an efficient and effective manner.